Principles of Antimicrobial Therapy

Disclosures and Special Request
Systemic Antibiotic Management of
Infection and Ocular Disease
Blair Lonsberry, MS, OD, MEd., FAAO
Diplomate, American Board of Optometry
Clinic Director and Professor of Optometry
Pacific University College of Optometry
[email protected]
8/12/13
Principles of Antimicrobial Therapy
•  Structural and biochemical
differences exist between
humans and
microorganisms.
Antimicrobial therapy takes
advantage of these
differences, e.g.
–  Bacterial cell wall
–  Bacterial ribosomes
Principles of Antimicrobial Therapy
•  Bacteriostatic vs. Bactericidal
drugs:
–  bacteriostatic drugs “arrest”
the growth and replication
of bacteria thus limiting
the spread of infection
while the body attacks.
–  bactericidal drugs kill
bacteria at serum
concentration levels
Paid consultant for:
•  Alcon Pharmaceuticals, Bausch and Lomb, Carl Zeiss
Meditec, Merck Pharmaceuticals, NiCox, SARCode
Special Request:
Interactive remotes don’t work on your TV, so please don’t
take them home! J
Commitment to change:
- write down three things that you “learned” from this
presentation that you can incorporate into your practice
to improve patient care
- revisit these points a month from now, again in 3
months and 6 months and see if you have adopted them
- make a commitment to change how you care for
patients!
Principles of Antimicrobial Therapy
•  Selection of an appropriate antimicrobial requires:
–  knowledge of the organisms identity,
–  its susceptibility,
–  site of infection,
–  patient factors,
–  safety of agent and
–  cost of therapy.
•  Often, the organism is not conclusively identified,
and the treatment is empirical.
–  the choice of agents in the absence of
confirmatory testing maybe guided by known
association of a particular organism with an
infection in a given clinical setting
Principles of Antimicrobial Therapy
•  Adequate levels of the antibiotic must reach the site of infection.
–  different tissues have variable permeability to the drugs.
–  natural barriers to drug delivery exist, such as prostate, CNS, brain and
vitreous.
•  Patient factors are crucial in drug selection. For example:
– 
– 
– 
– 
the status of patient’s immune system,
kidneys, liver, circulation,
age, gender, pregnancy, breast feeding,
allergies, etc.
1!
Principles of Antimicrobial Therapy
•  many of the antibiotics are minimally toxic
–  such as penicillins as they interfere with a site unique to
bacteria growth
•  others are reserved for life-threatening infections
because of potential for serious toxicity
–  e.g. chloramphenicol
•  cost of therapy also needs to be considered,
–  ie. if similar efficacy is achieved with a generic or less
expensive medication (or combo of meds) that may
increase compliance.
Chemotherapeutic Spectra
•  Narrow-spectrum antibiotics:
–  act only on a single or a limited group of
microorganisms, e.g. isoniazid active only against
mycobacteria.
•  Extended-spectrum antibiotics:
–  effective against gram + and significant number of
gram - bacteria, e.g ampicillin.
•  Broad-spectrum antibiotics:
–  effective against wide variety of microbial species (e.g.
tetracycline and chloramphenicol).
–  their use can drastically alter the bodies normal flora
(and result in superinfections)
Preventing Resistance
•  Just one organism, methicillin-resistant Staphylococcus aureus (MRSA), kills more
Americans every year (∼19,000) than emphysema, HIV/AIDS, Parkinson's disease,
and homicide combined
–  most serious MRSA infections, an estimated 85%, are associated with a
healthcare exposure, but nearly 14% of the infections are communityassociated.
•  Almost 2 million Americans per year develop hospital-acquired infections (HAIs),
resulting in 99,000 deaths the vast majority of which are due to antibiotic-resistant
pathogens
•  CDC: Get Smart: Know When Antibiotics Work
–  teaches both the provider and the patient when antibiotics should be used.
•  The IDSA suggests five to seven days is long enough to treat a bacterial infection
without encouraging resistance in adults, though children should still get the
longer course
–  this is different than previous guidelines of treating infections from 10-14 days.
8/12/13
Number of New Molecular Entity (NME) Systemic Antibiotics Approved by the US FDA Per Fiveyear Period, Through 3/11.
Shortage of New Antibiotics
•  In 2010, in recognition of the need for creative,
new ideas to address the antibiotic pipeline
problem and a measurable goal by which to
gauge progress, IDSA (Infectious Diseases
Society of America) launched the 10 × 20
initiative .
–  The 10 × ’20 initiative calls for the development of
10 novel, safe and effective, systemic antibiotics by
2020.
Infectious Diseases Society of America (IDSA) Clin Infect
Dis. 2011;52:S397-S428
© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases
Society of America. All rights reserved. For Permissions, please e-mail:
[email protected].
8/12/13
2!
New Class of Antibiotics
•  Fidaxomicin (Dificid) is the first of a new class of antibiotics
called macrocycles and was approved by the FDA in May 2011;
–  Optimer Pharmaceuticals
–  it’s a narrow-spectrum drug aimed specifically at Clostridium
difficile,
•  the bacterial, toxin-producing, potentially fatal infection of
the gut that occurs when broad-spectrum antibiotics have
killed off the other populations of bacteria that normally live
in the intestines
–  Fidaxomicin’s existing competition is vancomycin
•  as compared against vancomycin, fidaxomicin was
noninferior, in industry jargon
Ocular TRUST 3: Ongoing Longitudinal Surveillance
of Antimicrobial Susceptibility in Ocular Isolates
•  Background:
•  Ocular TRUST is an ongoing annual survey of nationwide
antimicrobial susceptibility patterns of common ocular
pathogens.
•  To date, more than 1,000 isolates from ocular infections have
been submitted to an independent, central laboratory for in vitro
testing.
•  Ocular TRUST, now in its third year, remains the only
longitudinal nationwide susceptibility surveillance program
specific to ocular isolates.
8/12/13
Ocular Trust 3: Results Ocular Trust 3
•  Antimicrobials tested represent six classes of drugs:
–  fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin,
moxifloxacin);
–  dihydrofolate reductase inhibitors (trimethoprim);
–  macrolides (azithromycin);
–  aminoglycosides (tobramycin);
–  polypeptides (polymyxin B); and
–  β-lactams (penicillin).
•  Staphylococci were classified as methicillin-resistant (MRSA) or
methicillin-susceptible (MSSA) based on susceptibility to
oxacillin.
OPHTHALMIC MRSA INFECTIONS IN THE PARKLAND HEALTH AND
HOSPITAL SYSTEM, 2000 – 2004
Blomquist, Trans Am Ophthalmol Soc 2006;104:322-345
1 million patients seen in the system from 2000-2004, with 3460 confirmed
MRSA infections!
!- of the total MRSA infections, 1.3% if them were ocular!
Ophthalmic Infection
Percent of Cases
Preseptal cellulitis
42%
Conjunctivitis
21%
Corneal ulcers
10%
Endophthalmitis
8%
Orbital cellulitis
2%
Other: e.g. dacrocystitis
10%
•  most antimicrobials, except penicillin and polymyxin B, continue
to be highly active against MSSA (azithromycin shows only
moderate activity)
•  with the exception of trimethoprim and tobramycin,
less than one-third of MRSA strains are susceptible
to ophthalmic antimicrobials
•  susceptibility profiles remain virtually identical for the
fluoroquinolones, regardless of methicillin phenotype
•  S. aureus is more susceptible to the fluoroquinolones than to
macrolides, as represented by azithromycin
Sites of An5microbial Ac5ons •  Antibiotics can be classified by their chemical structure, the
organisms they are effective against or by their site of action.
3!
Inhibitors of Cell Wall Synthesis
•  Human cells do not possess a cell wall like
bacteria do
Inhibitors of Cell Wall Synthesis
–  it is a very selective way to interfere with
bacterial growth.
•  To be maximally effective, the inhibitors
require actively proliferating bacteria
–  they are ineffective against non-dividing
bacteria.
•  The most important members of this
group are:
–  B-lactam antibiotics and
–  vancomycin.
B-­‐Lactam An5bio5cs •  This group includes:
–  penicillins,
–  cephalosporins,
–  carbapenems and monobactams.
•  B-lactamase inhibitors are sometimes added in
combination to reduce a bacteria s ability to
overcome the activity of the antibiotic
–  E.g potassium clavulanate (clavulanic acid)
Penicillins
•  This group includes the following commonly used members:
–  Amoxicillin (250/500 tid, 875 mg bid or extended release
775mg qd)
•  treatment of otitis media, sinusitis, and infections
caused by susceptible staph/strept involving upper and
lower respiratory tract, skin and urinary tract;
prophylaxis of infective endocarditis
•  Pediatric dosing:
– <3 months: oral 20-30 mg/kg/day divided q 12 hrs
– >3 months: oral 20-50 mg/kg/day divided 8-12 hrs
– >12 yrs: extended release 775 mg daily
Penicillins
•  Among the most widely effective and least toxic
–  increased resistance has limited their use
–  they are bactericidal
•  Interfere with the last step of bacterial wall
synthesis, resulting in cell lysis.
•  Therapeutic application in gram (+) cocci and
bacilli, gram (-) cocci, anaerobic, spirochetes
(syphilis).
•  The most common side effects include
hypersensitivity and diarrhea.
Penicillins: Dicloxacillin
–  Dicloxacillin (250-500 mg)
•  penicillinase resistant, used in penicillin resistant
staph
•  administer orally at least 1 hour before or 2 hours
after meals
•  Dosing:
– Children<40kg: 12.5-25 mg/kg daily divided
– Children>40kg: 125-250 mg q 6 hours
– Adults: 250 mg q 6 hours
4!
Penicillins Penicillins: Augmen5n Name
Treatment for
Administration
Penicillin G and V
All stages and forms of syphilis
Via IM or IV injection
Ampicillin
Prophylactic use in dental
Adults:
surgery patients
- 250-500 mg every 6 hours
Active against haemophilus and
salmonella
Nafcillin
Osteomyelitis, septicemia,
endocarditis and CNS
infections
IM/IV
Adults:
- 500 mg every 4-6 hours
Penicillins: Augmen5n •  Augmentin is very effective for skin and skin
structure infections such as:
•  dacryocystitis,
•  internal hordeola,
•  pre-septal cellulitis.
–  Treatment of:
•  otitis media,
•  sinusitis,
•  lower respiratory and urinary infections.
•  Augmentin is amoxicillin with potassium
clavulanate (clavulanic acid 125 mg).
•  Clavulanate is a B-Lactamase inhibitor which
reduces a bacteria s ability to negate the effect
of the amoxicillin by inactivating penicillinase
(enzyme that inactivates the antibiotic affect).
–  Dicloxacillin can also be used in infections due to
penicillinase-producing staph.
Penicillins: Augmen5n –  It has low:
•  GI upset,
•  allergic reaction and anaphylaxis.
–  Serious complications include:
•  anemia,
•  pseudomembranous colitis and
•  Stevens-Johnson syndrome.
–  Given prophylactically to dental surgery patients.
Penicillins: Augmentin.
Adults:
–  250-500 mg tab q 8hr (tid)
(also available in chewable
tablets and suspension)
–  or 875 mg q 12hr (bid)
–  1000 mg XR: q12 hr and
not for use in children <16
Peds: <3 mos 30mg/kg/day
divided q12hrs using
suspension
•  >3 mos 45-90mg/kg/day
divided q12hrs (otitis media
90mg for 10 days)
Sinusitis Red Eye
•  Sinus infections (rhinosinusitis), are an
inflammation of the nasal and sinus passages
that can cause uncomfortable pressure on either
side of the nose and last for weeks
•  The increase in mucus creates pressure in the
sinuses that leads to pain.
•  The sinuses surround the ocular region
–  pressure from sinuses may feel like eye
pressure.
–  swollen sinuses and nasal membranes can
push against ocular nerves resulting in pain.
•  Most develop during or after a cold or other
upper respiratory infection, but allergens and
environmental irritants may also trigger them
5!
Sinusitis Treatment
•  The infection is likely bacterial and should be
treated with antibiotics if:
–  symptoms last for 10 days without improvement, or
–  include fever of 102 degrees or higher,
–  nasal discharge and facial pain lasting three to four days
•  Because of increasing resistance to the antibiotic
amoxicillin — the current standard of care — the
ISDA recommends Augmentin
•  Augmentin 250/500 TID for 5-7 days for adults,
10-14 days for children
Penicillins: Hordeola:
•  Internal are secondary to a staph
infection of the meibomian glands
•  External are an infection of the Zeis or
Moll glands
–  Patients present with tenderness and
swelling of affected area.
•  Standard treatment includes:
–  good lid hygiene with warm compresses
and lid washes
–  Dicloxacillin 250 mg po QID for 7-10
days.
–  may consider topical AB ung on external
hordeolum.
Penicillins: Dacryocystitis
•  infection of the lacrimal sac
usually secondary to an
obstruction.
•  in pediatric patients:
–  the obstruction usually
resolves by age 9-12 months.
–  many pediatric
ophthalmologists will wait
until after this age to probe
the ducts to free the
obstruction.
Penicillins: Dacryocystitis
•  Dacryocystorhinostomy (DCR)
–  surgical procedure of choice.
–  allows for the bypassing of the
lacrimal duct apparatus as long
as the canalicular apparatus is
intact.
•  Punctal dilation and nasolacrimal
irrigation is contraindicated in the
acute stage due to the increased
risk of periorbital cellulitis.
Penicillins: Preseptal Celluli5s Penicillins: Dacrocystitis
•  Treatment includes:
–  Augmentin 500/125 mg (500
mg amoxicillin/125 mg
clavulanic acid) TID
•  or 875/125 mg BID for 7-10
days or
–  Dicloxacillin 250 mg po QID.
•  Infection and inflammation located
anterior to the orbital septum and
limited to the superficial periorbital
tissues and eyelids.
–  usually follows periorbital trauma or
dermal infection (suspect staph sp in
trauma).
–  eyelid swelling, redness, ptosis, pain and
low grade fever.
•  Tx:
•  Augmentin 500/125 mg TID
–  or 875/125 mg BID for 7-10 days or
–  if moderate to severe IV Fortaz
(ceftazidime) 1-2 g q8h.
6!
Cephalosporins
Cephalosporins •  Closely related structurally and functionally to the penicillins,
•  1st generation: cefadroxil (Duricef), cefazolin
• 
(Ancef), cephalexin (Keflex), and cephalothin
•  2nd generations: cefaclor (Ceclor), cefprozil,
cefuroxime (Zinacef), cefotetan, cefoxitin
•  3rd generation: cefnir, cefixime, cefotaxime
(Claforan), ceftazidime (Fortaz), ceftibuten,
ceftizoxime, ceftriaxone (Rocephin IM/IV).
•  4th generation: cefepime
•  Duricef, Keflex, Ceclor (all orally administered) are
effective against most gram positive pathogens
and especially good for skin and soft tissue
infections.
–  have the same mode of action,
–  affected by the same resistance mechanisms.
–  tend to be more resistant to B-lactamases.
•  classified as 1st, 2nd, 3rd, and 4th generation based largely on
their bacterial susceptibility patterns and resistance to Blactamases.
•  Should be avoided or used with caution in patients who are
allergic to penicillin (apprx 10% x-reaction with penicillin
allergy has been reported but thought to be much closer to
the 1-2%)
–  allergic response without allergy to penicillin
is 1-2%.
•  Typically administered IV or IM, poor oral absorption.
Cephalosporins: Hyperacute Conjunc5vi5s Cephalosporins •  Keflex (cephalexin):
–  treatment of respiratory, GI, skin and skin
structure, and bone infections as well as otitis media
–  Adults: 250-1000 mg every 6 hours
•  - typical dosing 500 every 6 hours
–  Children: 25-100 mg/kg/day divided 6-8 hours
•  Hyperacute conjunctivitis:
–  usually secondary to gonorrhea
or chlamydia.
•  profuse purulent discharge,
•  pain,
•  redness,
•  chemosis,
•  papillae,
•  positive nodes
Chlamydia
•  Chlamydia is the most frequently reported bacterial sexually
transmitted disease in the United States
•  Chlamydia is known as a "silent" disease because the majority of
infected people have no symptoms
•  if symptoms do occur, they usually appear within 1 to 3 weeks
after exposure
•  women who have symptoms might have an abnormal vaginal
discharge or a burning sensation when urinating
•  men with signs or symptoms might have a discharge from their
penis or a burning sensation when urinating
• men might also have burning and itching around the opening of the
penis.
8/12/13
Chlamydia: Treatment
•  Recommended Treatment Regimens:
–  Azithromycin 1 g orally in a single dose
•  OR
–  Doxycycline 100 mg orally twice a day for 7 days
•  Alternative Treatment Regimens:
–  Erythromycin base 500 mg orally four times a day for 7
days
•  OR
–  Erythromycin ethylsuccinate 800 mg orally four times a
day for 7 days
•  OR
–  Levofloxacin 500 mg orally once daily for 7 days
•  OR
–  Ofloxacin 300 mg orally twice a day for 7 days
8/12/13
7!
Chlamydia: Treatment
•  Azithromycin versus doxycycline:
•  for the treatment of genital chlamydial infection treatments were equally
efficacious
•  Azithromycin should always be available to treat patients for whom
compliance with multiday dosing is uncertain.
•  Levofloxacin and ofloxacin are effective treatment alternatives but
are more expensive and offer no advantage in the dosage regimen.
•  other quinolones either are not reliably effective against chlamydial
infection or have not been evaluated adequately
8/12/13
Gonorrhea
•  Some men with gonorrhea may have no symptoms at all
–  signs or symptoms appear 1 to 14 days after infection
–  signs and symptoms include a burning sensation when
urinating, or a white, yellow, or green discharge from the penis
–  sometimes men with gonorrhea get painful or swollen testicles.
•  In women, the symptoms of gonorrhea are often mild,
but most women who are infected have no symptoms.
–  symptoms can be so non-specific as to be mistaken for a bladder
or vaginal infection.
–  initial symptoms and signs in women include a painful or
burning sensation when urinating, increased vaginal discharge,
or vaginal bleeding between periods.
–  risk of developing serious complications from the infection,
regardless of the presence or severity of symptoms.
8/12/13
Gonorrhea Treatment • Adult cervical/urethral infection:
•  Ceftriaxone (Rocephin) IM injection of 250 mg in a
single dose
• If not an option then:
•  Cefixime (Suprax) 400 mg oral in a single dose
•  Alternative treatments include:
• Azythromycin 1 gram single dose
• Doxycycline 100 mg BID 7-10 days
• Neonatal: 25-50 mg/kg, up to 125 mg IV/IM
cetriaxone daily for 7 days.
• Syphilis, gonorrhea, chlamydia, chancroid, HIV
infection, and AIDS are reportable diseases in
every state.
Cephalosporins: Dacryocystitis
•  Dacryocystitis Tx:
•  Keflex 250-500 mg po QID,
•  In febrile cases:
•  IV cefazolin (Ancef) 1g
q8h or
• IV cefuroxime (Zinacef)
1.5g q8h.
Gonorrhea Conjunc5vi5s Treatment •  For patients with gonorrhea
conjunctivitis:
–  Single 250 mg IM
injection Ceftriaxone
(Rocehphin) or/
–  Cefixime (Suprax) 400
mg oral in a single dose
–  concurrent use of ocular
lavage and topical
fluoroqinolone
•  e.g. cipro/moxi/besi/
gatifloxacin q1-2 hrs
Cephalosporins: Dacryoadeni5s •  An inflammation or infection of the
lacrimal gland.
–  S&S include:
•  swelling of lid,
•  pain in area of swelling,
•  excess tearing or discharge and swelling of
lymph nodes.
•  maybe secondary to viral or
bacterial infection
•  Tx:
–  Keflex (cephalexin) 250-500mg po
QID,
–  for more severe cases IV cefazolin
(Ancef) 200mg/kg divided into 3
doses.
8!
Cephalosporins:
Preseptal Cellulitis Treatment
Cephalosporins:
Preseptal Cellulitis
•  infection and inflammation
anterior to the orbital septum
and limited to the superficial
periorbital tissues and eyelids.
–  Signs and Symptoms include:
•  eyelid swelling,
•  redness,
•  ptosis,
•  pain and
•  low grade fever.
•  Tx:
–  Mild:
•  Ceclor (cefaclor) 250-500mg
q8h
–  Moderate to severe:
•  IM Rocephin (ceftriaxone) 1-2
grams/day or
•  IV Fortaz (ceftazidime) 1-2 g
q8h.
Cephalosporins:
Orbital Cellulitis Treatment
Cephalosporins:
Orbital Cellulitis
•  infection and inflammation within the orbital cavity
producing orbital S&S.
•  most commonly secondary to ethmoid sinusitis.
•  Staph and Strept most common isolates.
•  Signs and Symptoms include:
–  decreased VA,
–  pain,
–  red eye,
–  HA,
–  diplopia,
–  bulging eye,
–  APD,
–  EOM restriction,
–  lid swelling and
–  fever (generally 102 degrees F or higher)
Cephalosporin: Endophthalmi5s •  Endophthalmitis:
•  intraocular infection involving anterior/
posterior segments usually secondary to
postoperative infection.
–  95% gram +ve bacteria including
•  staph (80%), strept (10%) with about 6% gram
–ve organisms.
•  Patients present with:
• 
• 
• 
• 
• 
• 
pain,
discharge,
decreased VA,
corneal edema,
KP s,
vitritis, etc.
photophobia,
red eye,
proptosis,
injection,
AC reaction,
IV Antibiotics for 7-10 days:
–  IV Ceftriaxone (Rocephin) 50 mg/kg/Q12h/day
OR
–  IV Cefotaxime (Claphoran)50 mg/kg/Q6h/day
PLUS
"  
IV clindamycin 40 mg/kg/day in 3 doses
IF PATIENT HAS A PENICILLIN
ALLERGY
–  IV vancomycin 30 mg/kg/day in 3 doses infused
over 90 minutes
•  Oral treatment 2-3 weeks post IV:
–  Amoxicillin-clavulanate 875 mg/125 mg PO
q12h or
–  Cefpodoxime 200 mg PO q12h or
–  Cefdinir 600 mg/day PO q 12h
Endophthalmitis Treatment
•  Intravitreal:
–  vancomycin 1 mg/0.1ml and ceftazidime (Fortaz) 2.25 mg/0.1 ml (or
amikacin),
•  Subconjunctival:
–  vancomycin 25mg and ceftazidime (Fortaz) 100mg (gentamicin) and
dexamethasone 12-24mg,
•  Topical:
–  fortified vancomycin (Vancocin HCl 2.5% Ophthalmic) and ceftazidime
(Fortaz) 50mg/ml/hr, topical steroid and cycloplegic,
•  controversial IV systemic AB.
9!
Vancomycin/Bacitracin
•  Vancomycin and bacitracin both inhibit cell wall synthesis.
•  Vancomycin is increasingly important as it is effective against
multiple drug-resistant organisms (such as MRSA/MRSE and
enterococci)
–  used in patients who have penicillin allergies
–  often considered the drug of last resort, though overuse has brought
about resistance.
•  Bacitracin is active against a wide variety of gram (+) organisms
–  restricted to topical use due to its potential for nephrotoxicity.
Vancomycin •  Orbital Cellulitis: Infection and
inflammation within the orbital
cavity producing orbital S&S.
Vancomycin •  Vancomycin is typically administered systemically as an infusion due to its
poor oral absorption
–  complications are minimized when it is administered
at less than 10 mg/min
•  topical fortified vancomycin can be compounded (25-50 mg/ml)
(Vancocin HCl 2.5% Ophthalmic Drops)
•  Complications include:
–  anaphylaxis (hypotension, wheezing, dyspnea,
urticaria, pruritis),
–  upper body flushing,
–  pain secondary to muscle spasm, nausea, diarrhea,
headache.
–  typically the most serious complication is
nephrotoxicity but it is an infrequent complication.
Vancomycin –  decreased VA, pain, red eye, HA,
diplopia, bulging eye, APD, EOM
restriction, lid swelling and fever.
•  Endophthalmitis: intraocular infection involving
anterior/posterior segments usually secondary to
postoperative infection.
–  present with pain, photophobia, discharge,
red eye, decreased VA, proptosis, corneal
edema, injection, KP s, AC reaction, vitritis,
etc.
•  IV ceftriaxone (Rocephin) 50 mg/kg/
Q12h/day or
•  Intravitreal vancomycin 1 mg/0.1ml and
ceftazidime 2.25 mg/0.1 ml (or amikacin),
•  IV cefotaxime (Claforan) 50 mg/kg/
Q6h/day
plus
–  IV vancomycin 30 mg/kg/day in 3
doses infused over 90 minutes
(penicillin allergy) or IV clindamycin
40 mg/kg/day in 3 doses .
•  subconj vancomycin 25mg and ceftazidime
100mg (gentamicin) and dexamethasone
12-24mg,
•  topical fortified vancomycin and ceftazidime
50mg/ml/hr, topical steroid and cycloplegic
Bacitracin •  Due to nephrotoxicity, bacitracin not
used as a systemic med.
•  Bacitracin useful for bacterial lid
disease (staph blepharitis)
–  has a low rate of allergy and
toxicity.
•  Primarily gram + activity so
usually found in combination with a
gram - compound
–  e.g. polymixin B (Polysporin).
PROTEIN SYNTHESIS
INHIBITORS
10!
Protein Synthesis Inhibitors
•  These antibiotics work by targeting the
bacterial ribosome.
–  they are structurally different from mammalian
ribosomes,
–  in higher concentrations many of these antibiotics
can cause toxic effects.
•  This group includes:
Tetracyclines
•  Nonresistant strains concentrate this antibiotic intracellularly resulting in
inhibition of protein synthesis.
•  Broad spectrum, bacteriostatic,
–  effective against gram (+) and (-) bacteria and against non-bacterial organisms
–  widespread resistance has limited their use.
•  Drug of choice for Rocky Mountain Spotted Fever, Cholera, Lyme disease,
mycoplasma pneumonia, and chlamydial infections.
•  Side effects include gastric discomfort, phototoxicity, effects on calcified
tissues, vestibular problems, pseudotumor.
–  (a) tetracyclines, (b) aminoglycosides, (c) macrolides,
–  (d) chloramphenicol, (e) clindamycin, (f)
quinupristin/dalfopristin and (g) linezolid
Tetracyclines •  This group includes:
Tetracyclines: Acne Rosacea •  Acne rosacea:
–  Tetracycline (250mg - 500 mg cap BID-QID) needs
to be taken 1 hour before or 2 hours after a meal.
–  Minocycline (100 mg cap BID)
–  Doxycycline (20mg - 100 mg cap or tab BID)
–  affects females>males after 30 with peak
incidence 4-7th decade of Celtic/Northern
European descent. Males more disfigured.
•  4 subtypes with classic signs of flushing,
papules or pustules usually in crops,
telangiectasia.
–  secondary ocular complications (85% of
patients) and often precede other skin
manifestations include erythema, itching and
burning.
•  Mainstay oral Tx is Oracea (40 mg in
morning) or
–  tetracycline 500 mg po BID or doxycycline
100 mg po BID or minocycline 100 mg po
BID for 4-12 wks.
–  NOTE: Oracea is subantimicrobial therapy
Acne Rosacea Treatments Oral Antibiotics
Topical Treatments
Non-Prescription
Erythromycin
metronidazole (Metrogel)
Rosacea-Ltd III
Tetracycline
BenzaClin (Clindamycin 1% &
benzoyl peroxide 5%)
ZenMed
Doxycycline
BenzaMycin (Erythromycin 3% &
benzoyl peroxide 5%)
Neova Therapy
Minocycline
tretinoin (Retin-A)
Kinerase
Clindamycin 1% lotion/gel
Rosacare
Plexion Cleanser/Lotion (Sulfa 10%
& sulfur 5%)
www.internationalrosaceafoundation.org!
Tetracyclines: Adult Inclusion Conjunc5vi5s –  occurs in sexually active adults
–  women are more susceptible than
men.
–  usually transmitted through hand-toeye spread of infected genital
secretions.
–  incubation period is one to two
weeks
•  Signs and Symptoms:
–  ocular irritation, watering,
mucopurulent discharge and
positive nodes
–  often a unilateral disease but can
involve both eyes
–  follicles inferior fornix, mixed
papillary/follicular on upper lid,
subepithelial infiltrates, SPK.
11!
Tetracyclines: Adult Inclusion Conjunc5vi5s Treatment •  If left untreated, resolves
spontaneously in 6-18 months
•  can be treated topically with
tetracycline, erythromycin, and
fluoroquinolones
–  due to the high prevalence of
concomitant genital tract infection,
systemic antibiotic therapy is
recommended
•  Mainstay oral treatment is:
–  Doxycycline 100 mg po BID for 7-10
days.
–  Topical AB therapy is done
concurrently.
Recent Case
21 yo Hispanic female
Chief Complaint: Red eye
– 
– 
– 
– 
– 
Quality: Painful irritation; progressing in severity
Duration: Started that same morning
Location: OD only
Relief: OTC allergy drop provides no relief (pt believed it to be allergies)
Associated symptoms: Throbbing pain, watering, no light sensitivity, no pain with
blinking
–  Severity: 7.5/10
•  PMHx: Asthma diagnosed 7-8 yrs prior. Inhaler PRN, usually once a
month. Heart murmur diagnosed at birth, without causing any
complications.
•  Allergies: NKDA
•  Medications: IUD for birth control
Examination
Aided VAs: OD 20/25 +1 OS 20/20 OU 20/20
OD SLE
–  Lid/Lashes: slight ptosis of UL, with swelling; mild mucous discharge
–  Palpebral Conjunctiva: 2+ follicles (inf), 1+ papillary rxn (sup + inf)
Anterior Chamber: Deep and quiet
IOP: OD: 18 OS: 21
Posterior pole unremarkable
Assessment/Plan
379.91 Pain In or Around Eye
Assessment
–  Photophobia, follicles, and papillary rxn
–  Mild mucous discharge, inferior fornix OD
Plan
–  1 gtt Durezol OU in-office
–  Pt education of iritis, symptoms, and course of
treatment
–  Dispensed sample of Tobradex ST q2h OU x 2-3 days
–  Rx Z-pak
RTC 1 – 2 days for red eye follow-up
Tetracyclines: Hordeola
•  Internal are secondary to a staph
infection of the meibomian glands,
while external are an infection of the
Zeis or Moll glands. Px present with
tenderness and swelling of affected
area.
•  Standard treatment includes:
–  good lid hygiene with warm compresses
and lid scrubs in conjunction with
–  doxycycline 50-100 mg po BID for 2-3
weeks.
–  may consider topical AB ung on
external hordeolum.
Tetracyclines: Meibomian Gland Dysfunction
•  Meibomian gland dysfunction:
–  also referred to as meibomitis and
patients experience dry eye problems
secondary to increased evaporation of
the tears.
–  signs include noticeable capping of the
glands and frothing of tear film.
•  Standard treatment includes:
–  good lid hygiene with warm
compresses and lid scrubs in
conjunction with
–  doxycycline 50 mg po BID for 2-3
months.
•  Erythomycin ung (Ilotycin) can also be used
externally.
12!
Tetracyclines: Recurrent Corneal Erosion
•  RCE:
–  repeated, spontaneous
disruption of corneal epi.
–  patient experiences foreign
body sensation, photophobia,
blepharospasm, decreased VA
and lacrimation upon waking.
–  History of trauma usually
reported or EBMD
Aminoglycosides
•  Previously were mainstay treatment for infections due to aerobic
gram (-) bacilli.
–  due to serious associated toxicities, they have been replaced by safer
antibiotics such as 3rd gen cephalosporins, fluoroquinilones, cilastin.
•  Effective in the treatment of infections suspected of being due to
aerobic gram (-) bacilli including Pseudomonas.
–  usually combined with B-lactam or vancomycin for anaerobic bacteria.
They are bacteriocidal!
•  Can have severe adverse effects including ototoxicity,
nephrotoxicity, delay in nerve conduction, and skin rash.
Aminoglycosides: Ocular Indica5ons •  Systemic aminoglycocides not
commonly indicated for ocular
conditions
–  amikacin has been used for
endophthalmitis IV and intravitreal
•  Topical preparations are widely used as
single agent preparations, in
combination with other antibiotics as
well as in combination with steroids.
Tetracyclines: Recurrent Corneal Erosion
•  Standard treatment includes:
–  bandage contact lens,
hyperosmotics
–  treat with doxycycline 50 mg po
BID for 2-3 months
•  include use of topical steroid
bid-tid for 6-8 weeks.
–  if recurrence still happen, consider
stromal puncture of affected area.
Aminoglycosides
•  This group includes:
–  Gentamicin
–  Neomycin
–  Streptomycin
–  Tobramycin
–  Amikacin
Macrolides
•  Erythromycin was the first of these drugs, as an alternative to
penicillin. Bacteriostatic though at [higher] maybe cidal
•  Macrolides bind to the bacterial ribosome and inhibit protein
synthesis.
–  have same spectrum of action as penicillins so are used in those patients
who are allergic to that group.
•  Resistance to erythromycin is becoming a serious clinical
problem.
•  Adverse effects include:
–  epigastric distress, jaundice, ototoxicity and contraindicated in patients
with hepatic disease.
13!
Macrolides
•  This group includes:
–  Erythromycin (125 or 250 mg cap, enteric coated) dosing
250mg q 6h or 500 q12h
–  Clarithromycin
–  Azithromycin (Z-pak) (500mg first day, then 250 mg for next 4
days)
–  Telithromycin
Recent New Report
•  A study published in a recent addition of the New England
Journal of Medicine, found patients prescribed Z-Pak were more
likely to die than those prescribed amoxicillin.
•  The results were especially pronounced for those who died of
heart attacks
•  Patients on azithromycin had two and a half times the odds of
dying from a cardiovascular than did patients on amoxicillin.
•  FDA Recommendation: those patients on azythromycin should
continue taking their medication
Macrolides
•  Azithromycin (Z-pak) is active against respiratory infections
due to H. influenzae and Moraxella.
–  it is a costly medication (generic now available),
–  now a preferred therapy for urethritis by chlamydia.
–  excellent for soft tissue infections.
–  use with caution in patients with impaired liver function
and no controlled studies for use in pregnancy.
Macrolide: Hyperacute Conjunctivitis
•  Hyperacute conjunctivitis:
–  usually secondary to gonorrhea
or chlamydia.
–  profuse purulent discharge,
pain, redness, chemosis, positive
nodes.
•  Tx: Azithromycin (Zithromax)
–  1 gram single oral dose.
•  concurrent use of ocular lavage and
topical fluoroqinolone (e.g. cipro//
moxi/besi/gatifloxacin q1-2 hrs).
Azithromycin and the Risk of Cardiovascular Death. Wayne A. Ray, Ph.D., Katherine T. Murray, M.D., Kathi Hall,
8/12/13
B.S., Patrick G. Arbogast, Ph.D., and C. Michael Stein, M.B., Ch.B. N Engl J Med 2012; 366:1881-1890
Macrolides: Adult Inclusion Conjunctivitis
•  Adult Inclusion Conjunctivitis:
–  occurs in sexually active adults
presenting with ocular irritation,
watering, mucopurulent discharge and
positive nodes.
–  follicles inferior fornix, mixed
papillary/follicular on upper lid,
subepithelial infiltrates, SPK.
•  Inclusion conjunctivitis:
–  Azithromycin 20 mg/kg (1 gram for
adult) as a single dose or
–  500 mg first day then 250 mg daily
for 4 days,
–  erythromycin 250 mg po QID for 14
days.
Macrolides: Ocular Indica5ons •  Erythromycin can be used as
alternative treatment in patient
with:
–  internal hordeola,
–  pre-septal cellulitis,
–  dacrocystitis
•  remember high incidence of
staph resistance.
14!
Macrolides: Ocular Indica5ons •  Erythromycin available in topical
ointment form
–  Ilotycin
–  for treatment of superficial
infections
•  blepharitis and prophylaxis
of ophthalmia neonatorum
Chloramphenicol
•  Active against a wide range of gram (+) and (-)
organisms.
–  because of its toxicity, its use is restricted to lifethreatening infections for which no alternative
exists.
•  Bacteriocidal and bacteriostatic depending on
the organism.
•  Adverse effects include hemolytic and aplastic
anemia.
AzaSite
•  Azythromycin ophthalmic solution 1%
•  Indicated for the treatment of bacterial
conjunctivitis
•  Delivery vehicle is DuraSite which forms a gel-like
matrix which enhances contact time to the ocular
surface
–  results in high drug concentration in a variety of ocular
tissues
–  drug concentration levels remain high for a sustained
period of time even after dosing stopped
Chloramphenicol: Ocular Indica5ons •  Systemic treatment rarely used for ocular
conditions.
•  Available in solution 0.5% and ointment 1%
(Chloroptic)
–  generally not used in the US but commonly used
abroad (Europe and Australia).
•  Effective against most ocular bacterial infections
but because of potentially fatal complications
should only be used as a last resort.
Inhibitors of Nucleic Acid Synthesis/
Function.
Inhibitors of Nucleic Acid
Synthesis/Function
•  The fluoroquinolones are the main group of antibiotics that
act in this fashion.
–  they enter the bacterium via passive diffusion and once
inside the cell inhibit the replication of bacterial DNA by
interfering with the action of DNA gyrase and
topoisomerase IV during bacterial growth and
reproduction.
•  Norfloxacin was the first member of this group and has been
rapidly followed by newer generations of drugs which offer
greater potency, a broader spectrum and a better safety
profile.
–  unfortunately, their overuse has already led to the
emergence of resistant strains.
15!
Inhibitors of Nucleic Acid Synthesis/
Function.
•  Rifampin is the other major member of this
group and is an inhibitor of RNA synthesis
•  Bactericidal
•  Is a broad spectrum antibiotic but is used
mostly in the treatment of TB
–  resistance is common
–  Rifampin is typically used in combination with
other anti-TB meds
–  has a new role in treatment of MRSA in
combination with fusidic acid.
Inhibitors of Nucleic Acid Synthesis/
Function.
•  Ciprofloxacin is the most frequently used fluoro in the US.
–  effective against many systemic infections, with the
exception of serious infections caused by
methicillin-resistant Staph aureus, the enterococci
and pneumococci.
–  it is used in treating infections caused by
enterobacteria (ex. travelers diarrhea) and drug of
choice for anthrax prophylaxis.
–  has good activity against pseudomonas, and may
have synergistic activity with B-lactams.
•  Resistance has developed due to mutations in both gyrase and
topoisomerase.
Ocular Indications
•  Hyperacute conjunctivitis (chlamydia): Oral or
IM fluoroquinolone (only indicated if unable
to use cephalosporin)
•  Cat Scratch Disease: ciprofloxacin 500-750 mg
po q 12h for 10-14 days.
•  Orbital cellulitis: IV ciprofloxacin
•  Majority of the use of fluoroquinolones in
ocular use is in the form of topical drops and
ointments. Used in all forms of infections and
prophylaxis in ocular surgeries.
Inhibitors of Nucleic Acid Synthesis/
Function.
•  All the fluoro are bactericidal, with activity
becoming more pronounced as the serum
[drug] increases.
–  in general, they are effective against gram(-) bacteria
including pseudomonas and haemophilus, and have
good activity against some gram (+) organisms such
as strept.
•  Common practice to classify the fluoro into
generations with nalidixic acid being 1st
generation.
Inhibitors of Nucleic Acid Synthesis/
Function.
•  The fluoro are generally very well tolerated
though some of the most common adverse
reactions include:
–  GI upset,
–  CNS problems (HA and dizziness),
–  phototoxicity,
–  liver toxicity, nephrotoxicity, and
–  connective tissue problems
•  should be avoided in pregnancy, nursing mothers and
children under age of 18
Fluoroquinolone: Hyperacute Conjunctivitis
Tx:
•  Gonorrhea: CDC in 2007 took
fluoros off potential treatment
due to resistance. They maybe
used in cases of proven
resistance to cephalosporins
•  Chlamydia: can use as
alternative therapy after
azythromycin and doxycycline
•  E.g. Ofloxacin: 300 mg orally twice a day
for 7 days or Levofloxacin 500 mg orally
once daily for 7 days
–  concurrent use of ocular lavage and
topical fluoroqinolone (e.g. cipro//
moxi/besi/gatifloxacin q1-2 hrs).
16!
Fluoroquinolone: Cat-Scratch Disease
•  Cat-scratch disease (Parinaud s):
infection with Bartonella
–  resulting in granulomatous
conjunctivitis with associated
preauricular lymphadenopathy,
–  neuroretinitis,
–  focal chorioretinitis.
•  Tx: e.g. oral ciprofloxacin 500 mg
or gatifloxacin or moxifoxacin
400mg,
–  IV fluoroqinolone.
–  concurrent use of ocular lavage and
topical fluoroqinolone (e.g. cipro//
moxi/gatifloxacin q1-2 hrs).
Ocular Fluoroquinolones
•  Besivance (besifloxacin 0.6%) is strictly an
ophthalmic preparation with no systemic
counterpart
–  thought to possibly reduce chance of resistance
development
–  has DuraSite as vehicle so forms a gel-like liquid on
the eye increasing contact time
–  animal data has shown possible increased activity
for MRSA
Ocular Fluoroquinolones
•  Commonly used in optometry
for treatment of bacterial
conjunctivitis and keratitis
–  standard of care for the
treatment of bacterial keratitis
–  FDA approved are Ciloxan,
Ocuflox, Iquix
•  most practitioners utilize newer
generation Vigamox, Zymar,
Besivance, Iquix (levofloxacin 1.5%)
(3rd gen though increased
concentration from previous Quixin
0.5% levofloxacin)
Ocular Fluoroquinolones
•  Allergan released a concentrated form of
gatifloxacin
–  Zymar is gatifloxacin 0.3% (currently discontinued)
–  Zymaxid is gatifloxacin 0.5%
•  Indicated for bacterial conjunctivitis
•  Alcon has released Moxeza which is same
concentration of moxifloxacin as Vigamox but with
an added ingredient to increase ocular contact time
–  Vigamox is 0.3% moxifloxacin
Inhibitors of Metabolism
Inhibitors of Metabolism
•  Folic acid is required for the synthesis of precursor
molecules for RNA, DNA and other compounds
necessary for cellular growth.
–  in the absence of folic acid, cells cannot grow or divide.
•  (a) Sulfonamides and (b) trimethoprim are folic
acid antagonists and interfere with an infecting
bacteria s ability to divide.
•  Compounding the two has made a synergistic
compound used for effective treatment of a variety
of bacterial infections.
17!
Sulfonamides
•  Sulfa drugs are seldom prescribed alone except in the developing
countries, where they are used because of their low cost and
efficacy in certain infections such as trachoma.
•  With the combination with trimethoprim, co-trioxazole there was
a renewed interest in the sulfa drugs.
•  Sulfa drugs are bacteriostatic,
–  active against selective enterobacteria in the urinary tract.
–  resistance exists is those bacteria that don’t synthesize folic acid and in
any PABA producing bacteria (purulent producing bacteria).
Sulfonamides: Ocular Indica5ons •  No common indications for systemic
sulfonamides (sulfadiazine is sometimes
used as adjunct therapy in toxoplasmosis
Tx) though topical preparations do exist.
•  Sulfa s have limited use due to resistance
and allergic reactions
–  used more by non-ophthalmic
providers.
•  Available in combination with steroids
–  ex. Blephamide
Trimethoprim: Ocular Indica5ons •  Combined with sulfa (Bactrim/Septra)
indicated for MRSA suspected infections
•  Trimethoprim is found in combination with
polymixin B in a topical eye drop.
–  Trimethoprim has both gram +/- activity but not
effective against pseudomonas so Polymixin B is
added.
•  Low rate of allergic and toxic reactions, and
approved for children >2 months.
Sulfonamides
•  Adverse effects include:
–  hypersensitivity reactions such as rashes,
–  angioedema,
–  Stevens-Johnson syndrome are fairly common.
–  may also result in nephrotoxicity, hemolytic anemia,
–  drug potentiation
•  Ex. increased effect of hypoglycemic effect of tolbutamide
or anticoagulent of warfarin
Trimethoprim and Pyrimethamine
•  Similar antibacterial spectrum as sulfonamides, though has a
20-50 fold more potent affect than the sulfonamides.
•  Trimethoprim maybe used on its own to treat acute UTI s and in
the treatment of bacterial prostatitis (fluor preferred though) and
vaginitis
–  been found to be an effective treatment option for MRSA
•  Pyrimethamine is used for prophylaxis and Tx of malaria.
•  Resistance does exist, and adverse affects include several blood
anemias which can be reversed by administering folinic acid.
Pyrimethamine: Ocular Indica5ons •  Toxoplasmosis chorioretinitis
(acquired) presents with:
–  decreased VA,
–  photophobia, floaters,
–  vascular sheathing,
–  full-thickness retinal necrosis,
–  fluffy, yellow-white retinal lesion
adjacent to old scars,
–  overlying vitreous reaction
(headlights in fog), and
–  anterior chamber reaction.
18!
Treatment
•  Pyrimethamine 25 mg po 1-2 times/day
(loading dose 75mg) and
–  sulfadiazine 1 g po 6hrs and clindamycin 300 mg po
6hrs.
Co-­‐Trimoxazole (Bactrim/Septra) •  Resistance is more difficult because has to
develop resistance to both drugs.
•  Adverse effects include:
–  severe potential for dermatologic reactions,
–  GI upset,
–  blood disorders, and
–  drug potentiation.
Co-­‐Trimoxazole (Bactrim/Septra) •  Combination of trimethoprim and
sulfamethoxazole
– shows greater antimicrobial activity
than equivalent quantities of either
drug alone.
•  Has broader spectrum of action than the
sulfa s and is effective in treating:
– UTIs and respiratory tract infections
– often considered for treatment of
MRSA skin infections
Co-Trimoxazole (Bactrim/Septra)
•  Available:
–  Bactrim/Septra tablets:
– contains 80 mg trimethoprim and 400 mg
sulfamethoxazole
– dosing 2 tablets every 12 hours
–  Bactrim DS/Septra DS (Double Strenth)
•  contains 160 mg trimethoprim and 800 mg
sulfamethoxazole
•  Dosing 1 tablet every 12 hours
Case
•  25 WF presents to ER with swollen
and painful RUL
–  started 2 days previously
–  medical and ocular history
unremarkable.
–  VA normal, EOM’s unrestricted,
pupils normal, CVF full, CT or
orbit reveals swelling anterior to
orbital septum.
Inhibitors of Cell Membrane
Function
19!
V: Inhibitors of Cell Membrane Func5on •  Isoniazid is the most potent of the anti-tubercular
drugs and interferes with the production of
mycobacterial cell walls.
•  Mycobacteria is a slow growing organism and
treatment is often required from 6 months to
several years.
Thank You!!!
–  due to poor compliance, resistance has developed and
therefore treatment is never given as a single agent.
•  Multi-drug therapy is given and maybe changed on
a regular basis in order to effectively treat the
patient.
8/12/13
20!